IL-1β、IL-6、IL-8、IL-12、TNF-α和IFN-α与儿童重症COVID-19及多系统炎症综合征的关联
Association of IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-α With Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome.
摘要(中文译文)
细胞因子谱可为评估包括SARS-CoV-2在内的感染性疾病炎症反应提供临床相关信息。然而，与儿童重症COVID-19相关的细胞因子阈值浓度以及与儿童多系统炎症综合征（MIS-C）相关的细胞因子模式仍缺乏充分表征。本研究旨在评估与儿童重症COVID-19和MIS-C相关的IL-1β、IL-6、IL-8、IL-12、TNF-α和IFN-α的血清水平及探索性阈值浓度，并表征儿童SARS-CoV-2感染不同临床形式中的细胞因子模式。该队列研究纳入200例实验室确诊SARS-CoV-2感染的儿童，包括轻型COVID-19（n=106）、中型COVID-19（n=72）和重型COVID-19（n=22），40例诊断为MIS-C的儿童，以及45例SARS-CoV-2 PCR和ELISA结果阴性的儿童。参与者年龄为1个月至17岁（6.47±5.53岁），入组时均未接种COVID-19疫苗。在住院后24小时内、治疗开始前，采用免疫酶法测定IL-1β、IL-6、IL-8、IL-12、TNF-α和IFN-α的血清浓度。与重型COVID-19相关的细胞因子包括IL-1β（截断值6.96 pg/mL）、IL-6（截断值68.37 pg/mL）、IL-12（截断值34.53 pg/mL）、TNF-α（截断值60.63 pg/mL）和IFN-α（截断值26.96 pg/mL）。所有测定的细胞因子在识别MIS-C方面均表现出足够的判别性能：IL-1β（截断值7.28 pg/mL）、IL-6（截断值100.64 pg/mL）、IL-8（截断值16.93 pg/mL）、IL-12（截断值34.91 pg/mL）、TNF-α（截断值80.19 pg/mL）和IFN-α（截断值30.56 pg/mL）。随机森林分析确定IL-1β和IL-8为对COVID-19严重程度分类具有最高模型衍生重要性的变量，而年龄和性别的模型衍生重要性低于细胞因子生物标志物。细胞因子谱可能有助于更细致地评估儿童SARS-CoV-2相关疾病中的高炎症免疫反应。然而，其在常规临床和实验室标志物之外的附加临床价值需要在更大的独立儿童队列中验证。
Abstract
The cytokine profile may provide clinically relevant information for assessing the inflammatory response in infectious diseases, including SARS-CoV-2. However, the threshold concentrations of cytokines associated with severe pediatric COVID-19 and cytokine patterns related to multisystem inflammatory syndrome in children (MIS-C), remain insufficiently characterized. This study aimed to evaluate serum levels and exploratory threshold concentrations of IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-α associated with severe pediatric COVID-19 and MIS-C, and to characterize cytokine patterns across different clinical forms of SARS-CoV-2 infection in children. The cohort study included 200 children with laboratory-confirmed SARS-CoV-2 infection, including mild COVID-19 (n=106), moderate COVID-19 (n=72), and severe COVID-19 (n= 22), 40 children diagnosed with MIS-C, and 45 children with negative PCR and ELISA results for SARS-CoV-2. Participants were aged 1 month to 17 years (6.47±5.53 years), and none had received a COVID-19 vaccine at the time of inclusion. Serum concentrations of IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-α were measured within the first 24 hours of hospitalization, before treatment initiation, using immunoenzymatic assays. Cytokines associated with severe COVID-19 included IL-1β (cut-off 6.96 pg/mL), IL-6 (cut-off 68.37 pg/mL), IL-12 (cut-off 34.53 pg/mL), TNF-α (cut-off 60.63 pg/mL), and IFN-α (cut-off 26.96 pg/mL). All measured cytokines demonstrated adequate discriminatory performance for identifying MIS-C: IL-1β (cut-off 7.28 pg/mL), IL-6 (cut-off 100.64 pg/mL), IL-8 (cut-off 16.93 pg/mL), IL-12 (cut-off 34.91 pg/mL), TNF-α (cut-off 80.19 pg/mL), and IFN-α (cut-off 30.56 pg/mL). Random Forest analysis identified IL-1β and IL-8 as variables with the highest model-derived importance for COVID-19 severity classification, whereas age and sex showed lower model-derived importance than cytokine biomarkers. Cytokine profiling may support a more nuanced evaluation of hyperinflammatory immune responses in pediatric SARS-CoV-2-associated disease. However, its additional clinical value beyond routine clinical and laboratory markers requires validation in larger independent pediatric cohorts.
如何引用
AMA
Kateryna Kozak, Halyna Pavlyshyn. Association of IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-α With Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome.. Biomarker insights. 2026; doi:10.1177/11772719261472145.
APA
Kateryna Kozak, Halyna Pavlyshyn (2026). Association of IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-α With Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome.. Biomarker insights. https://doi.org/10.1177/11772719261472145
GB/T 7714
Kateryna Kozak, Halyna Pavlyshyn. Association of IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-α With Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome.[J]. Biomarker insights, 2026 doi:10.1177/11772719261472145.
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